Genome Evolution between oral polio vaccine and coxsackie virus
Introduction Polio or poliomyelitis, is a crippling and potentially deadly infectious disease caused by the poliovirus, PV. The virus lives in the throat and intestinal tract; it can be spread through person-to-person contact with the stool of an infected person or through oral/nasal secretions. Most people infected with polio virus have no symptoms; however, for less than 1% who develop paralysis it may result in permanent disability and even death. Polio used to be very common in the United States and caused severe illness in thousands of people each year before polio vaccine was introduced in 1955. There are two types of vaccine that protect against polio: inactivated poliovirus vaccine(IPV) and oral poliovirus (OPV), OPV is an attenuated live virus vaccine which differs from wild type due to a small number of mutations. It can infect humans but does not affect the nervous system. IPV is given as an injection in the leg or arm, depending on the patient's age. Most people get polio vaccine when they are children. OPV has not been used in the United States since 2000 but is still used in many parts of the world. (1). A major concern about the oral polio vaccine is its ability to revert to a form that can achieve neurological infection and cause paralysis. Although this is a rare event, outbreaks of vaccine-associated paralytic poliomyelitis have been reported in some parts of the world.(1) Poliovirus Poliovirus belongs to the enterovirus family of small RNA viruses. There are 4 enterovirus groups: polioviurses, Coxsackie A and B viruses and echoviruses. More recently these have been reclassified into 4 species, Enterovirus A-D. Poliovirus, as well as some of the coxsackie A viruses are classified as enterovirus C. All of the enteroviruses are transmitted by the fecal-oral route. Poliovirus is a small virus composed of a non-segmented positive strand RNA genome of about 7500 nucleotides surrounded by an icosahedral capsid composed of four proteins: VP1-4. The viral genome consists of a single open-reading frame flanked by two non-coding regions (5'NC and 3'NC). Capsid proteins are encoded by the P1 genomic region and nonsctructural proteins are encoded by P2-P3 regions. Oral Polio Vaccine In 1988, the World Health Organization (WHO) established a program to eradicate poliomyelitis, based on massive vaccination campaigns with the oral polio vaccine (OPV). The vaccine is composed of live attenuated viruses of the three serotypes (Sabin strains 1-3), they can multiply to high titers only in the gastrointestinal tract. The major genetic determinants involved in the attenuation of three OPV strains are located in the 5'NC genomic regions and are known to affect the efficiency of genomic translation in neuronal cells. In addition, codons of capsid proteins are also implicated in attenuation. (3) Due to low vaccine coverage in some countries of the developing world, the disease has not been eradicated. The low vaccine coverage contributed to the emergence of pathogenic, vaccine-derived polioviruses (VDPVs) in 15 regions of the world. Poliovirus Evolution and Recombination Recomination can happen between different types of enteroviruses of the same species. This mechanism called genetic plasticity is implicated in the emergence of pathogenic recombinant circulating vaccine-derived polioviruses (cVDPVs), poliomyelitis outbreaks in several regions of the world with insufficient vaccination coverage. Most of these cVDPVs have mosaic genomes formed of mutated poliovaccine capsid sequences and part or all of the non-structural sequences from other human enteroviruses of species C (HEV-C), in particular coxsackie A viruses. A study in Madagascar showed that recombinant cVDPVs had been co-circulating in a small population of children with many different human enterovirus types. (2) Circulating Vaccine Derived Polioviruses Most cVDPVs are recombinants between PV and other human enteroviruses C. All cVDPVs have similar genomic features. The 5' half of the genome encodes capsid proteins that are found in OPV vaccine strains, but with more than 1% nucleotide substitutions. The 3' half the recombinant, which encodes the nonstructural proteins, originates from a coxsackie virus. The first cVDPV outbreak detected occurred in 2000-2001 in the island of Hispaniola, with 13 cases in the Dominican Republic and 8 cases in Haiti, including two fatal cases. The virus isolates were unrelated to any known wild PV (<82% VP1 nucleotide sequence identity), but closely related to the Sabin 1 OPV strain (98% VP1 sequence identity). The cVDPV recovered two of the most important biological properties of wild PV: the capacity to cause severe paralytic disease in humans and the capacity for extensive human-to-human transmission. These viruses were all recombinants presenting a 5'NC and capsid region sequences derived from Sabin 1, whereas most of the non-capsid sequences were derived from other HEV-s (figure 3). 4 different types of recombinant viruses were found, which is shown by the different types of crosshatching in the figure. Conclusions The ability of OPV to recombine with other enteroviruses complicated the use of an oral vaccine to eradicate polio in the world. Sequencing of isolates enables scientists to track the creation of new OPV strains. Analysis of this phenomenon should provide us with new insight into viral evolution. References 1. http://www.cdc.gov/vaccines/VPD-VAC/polio/default.htm 2. Combelas N et al. Recombination between Poliovirus and Coxsackie A Viruses of Species C: A Model of Viral Genetic Plasticity and Emergence. Viruses ''2011;''3:1460-1484 3. Rezapkin GV et al. Genetic stability of Sabin 1 strain of poliovirus: implications for quality control of oral poliovirus vaccine. Virology 1998;245(2):183-7